Soluble E-selectin Research Articles

Effects of intermittent exercise on biomarkers of cardiovascular risk in night shift workers.

Cathepsin L (CatL), cathepsin S (CatS), and arteriosclerosis adhesion molecules such as monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) are potent elastases implicated in human arterial wall remodeling. In this study, we aimed to evaluate the effects of intermittent exercise on the plasma concentrations of these cathepsins and arteriosclerosis adhesion molecules in night shift workers. Thirty male participants who were night shift workers (experimental group, n = 15; control group, n = 15) were included in this study. The experimental group performed an intermittent exercise at 10-min bouts (30 min per day), three days a week during 10 weeks. Body composition, blood pressure, and cardiovascular disease risk factors were measured. After intermittent exercise, significant group time interactions for body weight (p < .01) and body fat percentage (p < .01) were found. With regard to cardiovascular disease risk factors, group time interactions for CatL (p < .01), CatS (p < .01), MCP-1 (p < .05), sE-selectin (p < .01), and sVCAM-1 (p < .01) were significant. This study provides preliminary evidence to suggest that intermittent exercise may represent an effective intervention strategy for preventing atherosclerosis, thus leading to improved cardiovascular health in night shift workers.

Interrelationship of Multiple Endothelial Dysfunction Biomarkers with Chronic Kidney Disease

Background: The interrelationship of endothelial biomarkers and chronic kidney disease (CKD) has not been well studied. Objective: We investigated the association of multiple biomarkers of endothelial dysfunction with the risk and severity of CKD. Method: We measured asymmetric dimethylarginine (ADMA), L-arginine, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), von Willebrand factor (vWF), flow-mediated dilation (FMD), and nitroglycerin-induced dilation (NID) in 201 patients with CKD and 201 controls without CKD. Multivariable analyses were used to examine the interrelationship of endothelial biomarkers with CKD. Result: The multivariable-adjusted medians (interquartile ranges) were 0.54 (0.40, 0.75) in patients with CKD vs. 0.25 (0.22, 0.27) μmol /L in controls without CKD (p Conclusion: These data indicate that multiple dysfunctions of the endothelium were present among patients with CKD.

SE-cadherin serves as a diagnostic and predictive parameter in prostate cancer patients

BackgroundMeasurement of prostate-specific antigen (PSA) advanced the diagnostic and prognostic potential for prostate cancer (PCa). However, due to PSA’s lack of specificity, novel biomarkers are needed to improve risk assessment and ensure optimal personalized therapy. A set of protein molecules as potential biomarkers was therefore evaluated in serum of PCa patients.MethodsSerum samples from patients undergoing radical prostatectomy (RPE) for biopsy-proven PCa without neoadjuvant treatment were compared to serum samples from healthy subjects. Preliminary screening of 119 proteins in 10 PCa patients and 10 controls was carried out by the Proteome Profiler Antibody Array. Those markers showing distinct differences between patients and controls were then further evaluated by ELISA in the serum of 165 PCa patients and 19 controls. Uni- and multivariate as well as correlation analysis were performed to test the capability of these molecules to detect disease and predict pathological outcome.ResultsScreening showed that soluble (s)E-cadherin, E-selectin, MMP2, MMP9, TIMP1, TIMP2, Galectin and Clusterin warranted further evaluation. sE-Cadherin, TIMP1, Galectin and Clusterin were significantly over- and MMP9 under-expressed in PCa compared to controls. The concentration of sE-cadherin, MMP2 and Clusterin correlated negatively and that of MMP9 and TIMP1 positively with the Gleason Sum at prostatectomy. Only sE-cadherin significantly correlated with the highest Gleason pattern. Compared to serum PSA, sE-cadherin provided an independent and better matching predictive ability for discriminating PCas with an upgrade at RPE and aggressive tumors with a Gleason Sum ≥7.ConclusionssE-cadherin performed most favorably from a large panel of serum proteins in terms of diagnostic and predictive potential in curatively treatable PCa. sE-cadherin merits further investigation as a biomarker for PCa.

Longitudinal Association Between Endothelial Dysfunction, Inflammation, and Clotting Biomarkers With Subclinical Atherosclerosis in Type 1 Diabetes: An Evaluation of the DCCT/EDIC Cohort.

OBJECTIVEThere is considerable interest in identifying biomarkers that predict high risk for the development of macrovascular complications in patients with diabetes. Therefore, the longitudinal association between subclinical atherosclerosis as measured by internal carotid artery intima-media thickness (IMT) and acute-phase reactants, cytokines/adipokines, thrombosis, and adhesion molecules was examined.RESEARCH DESIGN AND METHODSBiomarkers were measured at four time points over 20 years in 886 DCCT/EDIC participants with type 1 diabetes. Four composite scores were created by combining z scores generated from within the data set of individual biomarkers: acute-phase reactants (fibrinogen, C-reactive protein), thrombosis (fibrinogen, active and total plasminogen activator inhibitor [PAI]-1), cytokines/adipokines (tumor necrosis factor receptor-1 and -2, active and total PAI-1, IL-6), and endothelial dysfunction (soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble E-selectin). Internal carotid IMT was measured at EDIC years 1, 6, and 12, with elevated IMT defined at each time point as being in the upper quintile of its distribution.RESULTSLogistic regression models indicate that while individual biomarkers were not predictive of or associated with subclinical atherosclerosis, composite scores of acute-phase reactants (odds ratio [OR] 2.78 [95% CI 1.42, 5.42]), thrombolytic factors (OR 2.83 [95% CI 1.45, 5.52]), and cytokines/adipokines (OR 2.83 [95% CI 1.48, 5.41]) measured at our final time point EDIC years 8–11 were associated with higher levels of atherosclerosis at EDIC year 12, but findings were not consistent at early time points. The endothelial dysfunction score was not appreciably predictive of or associated with subclinical atherosclerosis at any of the time points measured.CONCLUSIONSThe pathophysiologic relationship between higher biomarker levels and progression of subclinical atherosclerosis remains unclear.

Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

BACKGROUND:To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome.MATERIALS/METHODS:We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35).RESULTS:We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups.DISCUSSION:The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process.

Association between insulin-like growth factor 1 and biomarkers of endothelial dysfunction and vascular inflammation in obese women

Given its possible protective effect on vascular endothelial function, we hypothesized that the circulating level of insulin-like growth factor 1 (IGF-1) could be associated with biomarkers of endothelial dysfunction and vascular inflammation, i.e., soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin (sE-selectin) and high-sensitivity C-reactive protein (hs-CRP, in non-diabetic obese women. A total of 40 obese women (median age 35 (31-39) years; moderately obese I (n=21) body mass index (BMI) 30.0-34.9 kg/m2 and severely obese (n=19) BMI 35.0-39.9 kg/m2) and 40 controls, age-matched healthy nonobese women were included in the study. Anthropometric parameters (BMI, waist circumference, fat adipose tissue percentage ? FAT% measured by bioelectrical impedance analysis), serum concentrations of biomarkers (IGF-1, sICAM-1, sE-selectin and hs-CRP) and common carotid artery intima-media thickness Z-score (CCIMT Z-score) were assessed in all subjects. Severely obese subjects had a significantly lower median concentration of IGF-1 compared to moderately obese and nonobese subjects (95 (73.75-109.25) vs. 120 (108.3-141.7) vs. 115.5 (94.1-165.5) mg/mL, P&lt;0.05). In moderately obese subjects, the median concentration of hs-CRP (3.41 (2.3-5.1) vs. 5.9 (3.2-9.57) mg/L, P=0.01) and sICAM-1 (244.5 (192.7-262.2) vs. 325.2 (229.2-339.6) mg/L, P=0.03) were significantly lower compared to severely obese subjects. In regression analysis IGF-1 concentration was independently associated with FAT% (?=-3.14; P=0.03), hs-CRP (?=-4.24; P=0.001) and CCIMT Z-score (?=-19.2; P=0.001). The circulating level of IGF-1 is associated with hs-CRP, but not with sE-selectin and sICAM-1 in non-diabetic obese women.

Differential Associations between CDH13 Genotypes, Adiponectin Levels, and Circulating Levels of Cellular Adhesive Molecules.

CDH13 gene variants with lower adiponectin levels are paradoxically associated with a more favorable metabolic profile. We investigated the statistical association between CDH13 locus variants and adiponectin levels by examining 12 circulating inflammation marker levels and adiposity status in 530 Han Chinese people in Taiwan. After adjustments for clinical covariates, adiponectin levels were positively associated with soluble vascular cell adhesion molecule-1 (sVCAM1) levels and negatively associated with adiposity status and levels of C-reactive protein (CRP), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM1). In addition, minor alleles of the CDH13 rs12051272 polymorphism were found to have lower adiponectin levels and higher CRP, sE-selectin, sICAM1, and sVCAM1 levels as well as higher body mass indices and waist circumferences in participants (all P < 0.05). In a subgroup analysis stratified by sex, significant associations between CDH13 genotypes and sE-selectin levels occurred only in men (P = 3.9 × 10−4 and interaction P = 0.005). CDH13 locus variants and adiponectin levels are associated with circulating levels of cellular adhesion molecules and adiposity status in a differential manner that interacts with sex. These results provide further evidence for the crucial role of adiponectin levels and CDH13 gene variants in immune-mediated and inflammatory diseases.

The role of selectins in alopecia areata.

IntroductionOne of the main histopathological features of alopecia areata (AA) is a lymphocytic infiltration that surrounds hair follicles. Soluble forms of E, L, P-selectins are known indicators of ongoing inflammation. There are no studies regarding the assessment of their contribution in AA.AimTo assess serum concentrations of selectins (E-selectin, L-selectin and P-selectin) in patients with AA in relation to selected clinical parameters, including disease severity and activity.Material and methodsSixty-four patients with AA were involved in the study. The diagnosis was based on physical examination and photodermoscopy. The control group consisted of 40 healthy subjects. The serum concentrations of soluble E-selectin, L-selectin and P-selectin were detected with ELISA method.ResultsStatistically significantly higher levels of E, P, L-selectins were found in AA patients as compared with the healthy group. Serum concentrations of soluble forms of E- and L-selectins correlated with the severity of the disease, while E-selectin with activity of AA.ConclusionsThis study shows that selectins may play an important role in the pathogenesis of AA and may be a target of future therapies in this disease.

Pan-Selectin Antagonist Rivipansel (GMI-1070) Reduces Soluble E-Selectin Levels While Improving Clinical Outcomes in SCD Vaso-Occlusive Crisis

Introduction: The pan-selectin antagonist rivipansel (GMI-1070) reduced intravascular arrest of red/white blood cell aggregates and improved blood flow and survival in a mouse model of sickle cell disease vaso-occlusive crisis (SCD VOC). In a Phase 1 study of GMI-1070 infusion in SCD adults at steady state (not in VOC), GMI-1070 decreased markers of cellular activation including neutrophil integrins, platelet/neutrophil aggregates, soluble adhesion molecule concentration; and markers of hemostatic activation. Furthermore, in a randomized Phase 2 study of SCD patients, treatment of VOC with GMI-1070 improved clinical outcomes such as time to resolution of crisis, time to discharge, and IV opioid use. Herein we report on the effect of GMI-1070 on biomarkers of cellular and hemostatic cascade activation from this Phase 2 trial.Methods: Patients in VOC enrolled in a prospective, randomized multi-center double-blind Phase 2 trial, ages 12-60 with HbSS or HbSB0thalassemia were treated with GMI-1070 q12h or placebo, in addition to standard treatment per institutional practice, until resolution of VOC. Clinical outcomes and pharmacokinetics have been previously reported (ASH 2013 Abstracts 775, 776, and 2206). Biomarker blood samples were drawn prior to study drug, and on a sparse sampling basis at times starting 30 minutes after initial dose and continuing until 36 hours after the last dose. Analytes measured included: soluble adhesion molecules E-selectin (sEsel), P-selectin, L-selectin, intercellular adhesion molecules 1 and 3, vascular cell adhesion molecule-1; and tissue factor and thrombin-antithrombin complexes by ELISA. At some sites, surface expression of monocyte b2 integrins MAC-1 & LFA-1 and platelet-monocyte aggregates were also measured by flow cytometry. Comparisons were made between the GMI-1070 and placebo groups, and serial expression levels were compared over time. Subgroup analyses were performed by hydroxyurea (HU) use, age group, baseline WBC, and 'responders’ based on clinical outcomes. A mixed effect model was used to test the LS means difference at each time point and ANCOVA model was used to analyze the nadir, peak, and last dose values.Results: ELISA and flow cytometry samples were collected from 70 and 15 subjects, respectively. Soluble E-selectin levels were reduced for the group on GMI-1070 compared to placebo throughout hospitalization, and the differences were statistically significant at some time-points (Figure 1). Baseline sEsel levels were similar; but the peak, nadir, and level at last dose were all lower in the GMI-1070 group (Figure 2). Exploratory subgroup analysis by HU use, age group, response as measured by visual analog scale or opiate use, frequency of VOC in the past, and baseline white blood cell count revealed consistently lower sEsel levels in the GMI-1070 group. Many, but not all, of these differences reached statistical significance.Conclusion: GMI-1070 use during VOC resulted in consistent and significant reductions of sEsel, overall and in sub-groups as compared to placebo. These findings are consistent with the hypothesized effect of GMI-1070 on endothelial activation and/or apoptosis, mediated by inhibition of E-selectin, although an effect on sEsel clearance cannot be excluded. A Phase 3 study is planned to evaluate efficacy and safety of GMI-1070 as treatment for VOC. Soluble E-selectin concentrations may be useful as a biomarker of pharmacodynamic effect. [Display omitted] [Display omitted] DisclosuresWun:GlycoMimetics: Research Funding; Pfizer: Steering Committee, Steering Committee Other; Emmaus Medical: Consultancy. Telen:GlycoMimetics: Research Funding; Pfizer: Consultancy; Dilaforette: Research Funding. Krishnamurti:GlycoMimetics: Research Funding. McCavit:GlycoMimetics: Research Funding; Pfizer: Consultancy. DeCastro:GlycoMimetics: Research Funding. Flanner:GlycoMimetics: Employment, Equity Ownership. Kuypers:GlycoMimetics: Research Funding. Larkin:GlycoMimetics: Research Funding. Rhee:GlycoMimetics: Consultancy. Magnani:GlycoMimetics Inc.: Employment, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees. Thackray:GlycoMimetics: Employment, Equity Ownership.

Diagnostic value of soluble E-selectin and highly sensitive C-reactive protein as markers for neonatal sepsis

Diagnostic value of soluble E-selectin and highly sensitive C-reactive protein as markers for neonatal sepsis

Pentraxin 3 as a biomarker of local inflammatory response to vascular injury in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with organ injury related to vasculitis. Inflammation of blood vessels results from auto-immunological activation of endothelial cells. The pentraxin 3 (PTX3), might act as an indicator of vasculitides in many diseases. The aim of this study was to determine whether PTX3 might be useful as a marker of vascular injury in SLE. This study was carried out in a group of 56 SLE women, and in the 28 female volunteers control group. All participants’ plasma and serum samples were collected to estimate concentrations (ELISA) of PTX3, soluble thrombomodulin, soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble form of vascular cell adhesion molecule 1 (sVCAM-1), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble platelet endothelial cell adhesion molecule 1, monocyte chemotactic protein-1 (MCP-1) and von Willebrand factor (vWF) activity. Anthropometric, demographic and lifestyle characteristics of SLE patients were also performed. The SLE patients had higher PTX3, vWF, MCP-1, sE-selectin and sVCAM-1 levels than the controls (1.82 ± 1.56 ng/mL, 237 ± 101%, 70.05 ± 18.31 ng/mL, 111.16 ± 49.15 ng/mL and 978.78 ± 462.35 ng/mL vs. 0.86 ± 0.40 ng/mL, 138 ± 43%, 58.56 ± 13.91 ng/mL, 66.04 ± 27.18 ng/mL and 499.07 ± 125.67 ng/mL, respectively). The independent factors affecting PTX3 expression included Systemic Lupus Erythematosus Disease Activity Index, prednisone dose and anemia severity. Moreover, the PTX3 areas under the curve–receiver operating characteristics curves 0.717 ± 0.056 with cut-off level of 1.96 ng/mL was comparable to vWF, MCP-1, sE-selectin, sP-selectin and sICAM-1. PTX3 and sVCAM-1 were the only factors related to SLE activity. Other vascular injury indicators associated with PTX3 were vWF and sVCAM-1. In conclusion, PTX3 concentrations in SLE patients might serve as a indicator of the activation/dysfunction of vascular endothelium.

Intercellular adhesion molecule 1 and progression of percent emphysema: The MESA Lung Study

Endothelial intercellular adhesion molecule (ICAM) 1 binds neutrophils and facilitates their transmigration into the lung; E-selectin facilitates leukocyte rolling. As neutrophils contribute to tissue destruction in emphysema and chronic obstructive pulmonary disease, we hypothesized that soluble ICAM-1 (sICAM-1) and E-selectin (sE-selectin) would be associated with longitudinal progression of emphysema and lung function decline. The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants 45-84 years old without clinical cardiovascular disease in 2000-02. The MESA Lung Study assessed percent emphysema (<-950 Hounsfield units) on cardiac (2000-07) and full-lung CT scans (2010-12), and spirometry was assessed twice over five years. sICAM-1 and sE-selectin were measured at baseline. Mixed-effect models adjusted for demographics, anthropometry, smoking, C-reactive protein, sphingomyelin and scanner factors. Among 1865 MESA Lung participants with measurement of sICAM-1 and percent emphysema the mean log-sICAM-1 was 5.5±0.3ng/mL and percent emphysema increased 0.73 percentage points (95% CI: 0.34, 1.12; P<0.001) over ten years. A one SD increase in sICAM-1 was associated with an accelerated increase in percent emphysema of 0.23 percentage points over ten years (95% CI: 0.06, 0.39; P=0.007). No significant association was found for sE-selectin, or between any adhesion molecule and lung function. Higher levels of sICAM-1 were independently associated with progression of percent emphysema in a general population sample.

Long-Term Exposure to Air Pollution and Markers of Inflammation, Coagulation and Endothelial Activation: a Repeat Measures Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA)

Air pollution is associated with cardiovascular disease (CVD) and systemic inflammation is posited to mediate this effect. Animal, experimental and epidemiologic studies suggest increases in short-term air pollution cause an inflammatory response. Much of the past literature has focused on the association between short-term air pollution exposure and markers of inflammation and coagulation. We assessed both the association between long- and short-term exposure to air pollution and markers of inflammation, coagulation and endothelial activation. We studied participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with repeat measures of serum C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, D-dimer, soluble E-selectin and soluble Intercellular Adhesion Molecule-1 (sICAM-1). We estimated associations of these markers with long-term ambient fine particulate matter (PM2.5), individual-level ambient PM2.5 (integrating indoor concentrations and time-location data), oxides of nitrogen (NOX), nitrogen dioxide (NO) and black carbon averaged over the year prior to blood draw. Short-term concentrations of PM2.5 reflected day of blood draw, prior day, and moving average of prior 2, 3, 4, and 5 day periods. CRP, IL-6 and D-Dimer were log-transformed. A random effects model was used to account for within-person clustering. After controlling for confounders, a 5 µg/m3 increase in long-term ambient PM2.5 was associated with a 5.53% higher IL-6 level (95% CI: 1.83, 9.36) and a 40 ppb increase in long-term NOx was associated with 7.07% higher level in D-dimer (95% CI: 1.62, 12.83). CRP, E-selectin and sICAM-1 showed little association with long-term air pollution and associations between short-term ambient PM2.5 and blood markers was largely null. These data are consistent with the hypothesis that associations between long-term exposure to air pollution are related to inflammation and fibrinolysis.

Soluble adhesion molecules as markers of native arteriovenous fistula thrombosis in children on uremia.

Vascular access represents a lifeline for children undergoing hemodialysis. A failure of vascular access among patients receiving regular hemodialysis is associated with increased morbidity, mortality and costs. We assessed the possibility of using soluble adhesion molecules as reliable predictors of vascular access failure in children on hemodialysis. Moreover, we evaluated whether there is an association among the different studied adhesion molecules in hemodialysis patients with thrombosed and non-thrombosed arteriovenous fistula fistulas (AVFs). This study included 55 hemodialysis children, 36 with good access and 19 with access failure, and 20 healthy volunteers. Forty-four patients had native AVFs and 11 patients had tunneled permanent catheter (11with thrombosed and 33 with non-thrombosed AVFs). Serum-soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) were measured using ELISA technique. A significant increase was found in the levels of sVCAM-1, sICAM-1, sE-selectin and sP-selectin versus controls and all hemodialysis patients, hemodialysis patients with good access and hemodialysis patients with access failure (P=0.001 for sVCAM-1 and sICAM-1 and P=0.0001 for sE-selectin and sP-selectin). A significant increase was found in the levels of sVCAM-1, sE-selectin and sP-selectin in both chronic hemodialysis patients with thrombosed and non-thrombosed native AVFs versus controls (P=0.0001 for all parameters). There was significant difference between both chronic hemodialysis patients with thrombosed and non-thrombosed native AVFs as regard to sVCAM-1 (54.64±30.82 versus 25.69±27.96ng/ml, P=0.04). Both sICAM-1 and sP-selectin were positively correlated with the erythropoietin (EPO) dose in hemodialysis children (r=0.31, P=0.04 and r=0.32, P=0.04, respectively). A significant positive association was found between E-selectin and sP-selectin in hemodialysis patients with thrombosed AVFs (r=0.83, P=0.04). There was a significant correlation between sVCAM-1 and EPO dose in thrombosed AVF group (r=0.84, P=0.01). The assessment of serum sVCAM-1 might be useful for the identification of the chronic hemodialysis patients at an increased risk for native AVFs thrombosis. The role of EPO in vascular access failure should be taken into consideration. The clinical relevance of these observations warrants further investigations.

The Association Between Bereavement and Biomarkers of Inflammation

Bereavement is a major life event that has been associated with a range of negative health outcomes. To assess whether levels of inflammation markers and cortisol vary significantly by bereavement status and/or number of recent bereavements. The study was based on a secondary analysis of data from the Midlife in the United States (MIDUS) II biomarkers project. After excluding participants suffering from conditions which directly affect immune functions, 529 participants were included (age 34–84 years), of whom 260 experienced the death of a person close to them 5–63months prior to assessment. Levels of interleukin 6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-I), Soluble E-selectin (sE-selectin) and cortisol were examined controlling for demographic and health characteristics. Bereaved respondents had higher levels of inflammatory biomarkers IL-6 and sE-selectin, but not CRP and sICAM-I than the non-bereaved. Number of recent bereavements significantly predicted levels of IL-6 in the unadjusted and adjusted regression models. Body Mass Index (BMI) and number of chronic conditions partially mediated the association between number of bereavements and IL-6 levels. Number of recent bereavements is associated with higher levels of inflammation, particularly among individuals with higher BMI and/or chronic health problems.

Systemic levels of the endothelium-derived soluble adhesion molecules endocan and E-selectin in patients with suspected deep vein thrombosis.

The initial evaluation of patients with suspected deep vein thrombosis includes the use of biomarkers reflecting activation of the coagulation system. However, the thromboembolic process and neighboring inflammatory responses also affect endothelial cells, and endothelial cell markers may therefore be altered by the disease. In the present population-based single-center study, we investigated the plasma levels of the endothelium-specific biomarkers soluble E-selectin and endocan in a consecutive and unselected group of 120 patients admitted to hospital for suspected deep vein thrombosis. Blood samples were collected when patients arrived at the hospital. DVT patients showed evidence for an acute phase reaction with increased serum C-reactive protein levels, but this was similar to many other patients admitted with suspected but not verified thrombosis. Plasma endocan and E-selectin levels did not differ between patients with thrombosis, healthy controls and the patients without verified thrombosis (i.e. patients with other causes of their symptoms, including various inflammatory and non-inflammatory conditions). However, the combined use of endothelial biomarkers, C-reactive protein and D-dimer could be used to identify patient subsets with different frequencies of venous thrombosis. Thus, analysis of plasma biomarker profiles including endothelial cell markers may be helpful in the initial evaluation of patients with deep vein thrombosis.

Off-pump CABG surgery reduces systemic inflammation compared with on-pump surgery but does not change systemic endothelial responses: a prospective randomized study.

Coronary artery bypass graft (CABG) surgery can result in severe postoperative organ failure. During CABG surgery, cardiopulmonary bypass (CPB) with cardiac arrest is often used (on-pump CABG), which often results in a systemic inflammatory response. To reduce this inflammatory response, off-pump CABG was reintroduced, thereby avoiding CPB. There is increasing evidence that the endothelium plays an important role in the pathophysiology of organ failure after CABG surgery. In this study, 60 patients who were scheduled for elective CABG surgery were randomized to have surgery for on-pump or off-pump CABG. Blood was collected at four time points: start, end, 6 h, and 24 h postoperatively. Levels of inflammatory cytokines, soluble adhesion molecules, and angiogenic factors and their receptors were measured in the plasma. No differences were found in preoperative characteristics between the patient groups. The levels of tumor necrosis factor-α, interleukin 10, and myeloperoxidase, but not interleukin 6, were increased to a greater extent in the on-pump CABG compared with off-pump CABG after sternum closure. The soluble endothelial adhesion molecules E-selectin, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 were not elevated in the plasma during and after CABG surgery in both on-pump and off-pump CABG. Angiopoietin 2 was only increased 24 h after surgery in both on-pump and off-pump CABG. Higher levels of sFlt-1 were found after sternum closure in off-pump CABG compared with on-pump CABG. Avoiding CPB and aortic cross clamping in CABG surgery reduces the systemic inflammatory response. On-pump CABG does not lead to an increased release of soluble endothelial adhesion molecules in the circulation compared with off-pump CABG.

Association of hsCRP and soluble fraction of E-selectin with diabetic and non-diabetic individuals

doiBackground and aims: It is known that endothelial dysfunction and low-grade inflammation are important element of diabetic complications. The soluble E-selectin is a marker of endothelial dysfunction and C-reactive protein is the most important inflammatory marker. The present study is done to investigate the effect of diabetes on these two markers. Methods: The present hospital based case control study was conducted in the department of Biochemistry with the collaboration of department of Medicine of Burdwan Medical College, Burdwan, west Bengal India. All subjects were selected by simple random sampling between March 2011 and May 2013. Blood level of these soluble E-selectin and high sensitive C-reactive protein were measured in two hundred diabetic and two hundred age, sex and other non-modifiable as well as modifiable risk factors matched non-diabetic healthy controls. Results: Compared with control value of high sensitive C-reactive protein and soluble E-selectin levels were higher in diabetic subjects (p &lt; 0.001). Our present study shows that levels of adhesion molecules and high sensitive C-reactive protein were higher in diabetic than non-diabetic. Conclusion: These data suggested that an increased level of inflammatory markers and adhesion molecules among diabetic compared with non-diabetic subjects. This suggests that chronic uncontrolled hyperglycemia contributes to progression of atherosclerosis associated with life-threading complications in middle-aged diabetic patients. DOI: http://dx.doi.org/10.3126/jaim.v3i1.10697 Journal of Advances in Internal Medicine 2014;03(01):17-22

Expression of growth‑regulated oncogene‑1, hepatocyte growth factor, platelet‑derived growth factor‑AA and soluble E‑selectin and their association with high‑risk human papillomavirus infection in squamous cell carcinoma of the uterine cervix.

The aim of the present study was to evaluate the clinical significance and prognostic value of growth‑regulated oncogene‑1 (GRO‑1), hepatocyte growth factor (HGF), platelet‑derived growth factor‑AA (PDGF‑AA), soluble E‑selectin (sE‑selectin) and high‑risk human papillomavirus (HPV; types 16, 18/45, 31 and 33/52/58/67) infection in cervical squamous cell carcinoma (CSCC). A total of 426cases were enrolled in the present study, of which 292cases were patients with CSCC, 43 were patients with cervical intraepithelial neoplasia (CIN) and 91were healthy controls. Luminex xMAP technology was used to detect the serum levels of GRO‑1, HGF, PDGF‑AA and sE‑selectin in all cases and two‑channel fluorescence quantitative polymerase chain reaction was used to determine HPV DNA in cervical scrapings from CSCC and CIN patients. The results demonstrated that the serum levels of GRO‑1, HGF and sE‑selectin were significantly higher in patients with CSCC compared with patients with CIN and the healthy controls (P<0.0001). Compared with the CIN patients, the HPV positive rate in the CSCC patients significantly increased (P=0.013). The four factors were correlated with certain clinicopathological variables of CSCC patients to a certain degree (P<0.05) and the levels of HGF were closely associated with HPV infection (P=0.039). The receiver operating characteristic curves demonstrated that HGF obtained the highest diagnostic value compared with the other three factors. Multivariate Cox regression analysis demonstrated that the serum levels of HGF (P<0.0001), FIGO stage (P<0.0001) and pelvic lymph node metastasis (P=0.001) were independent prognostic factors in patients with CSCC, while high‑risk HPV infection did not show any significance in this analysis. These results demonstrated that HGF may be a useful prognostic biomarker rather than high‑risk HPV types in patients with CSCC.

SAT0016 Correlation of Carotid Intimal Plaque in SLE with Non-Traditional Serum Biomarkers

BackgroundLupus patients have a strikingly increased risk of premature atherosclerosis and fatal cardiovascular events. This predisposition is neither fully accounted for by traditional cardiovascular (CV) risk factors nor SLE disease...